Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet

Brent J.F. Hill, Joseph L. Dixon, Michael Sturek

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Intracellular Ca2+ store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca2+ uptake into intracellular Ca2+ stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks - (1) low fat fed (control); (2) hyperlipidemic (F); (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the myoplasmic Ca2+ (Cam) response measured using single cell fura-2 imaging. The Cam response to caffeine (5 mM to release Ca2+ from the sarcoplasmic reticulum, SR) and ionomycin (10 μM; to release the total Ca2+ store) was determined in either the presence of low Na (19Na; inhibits Na+-Ca2+ exchange), thapsigargin (TSG; inhibits the SR Ca2+ pump), and a 19Na + TSG solution. Low Na induced the uptake of Ca2+ into both SR and non-SR Ca2+ stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca2+ store with TSG, 19Na evoked Ca2+ uptake into non-SR Ca2+ stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca2+ by SR and non-SR Ca2+ stores in diabetic dyslipidemic pigs.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalAtherosclerosis
Volume159
Issue number1
DOIs
StatePublished - Nov 10 2001
Externally publishedYes

Keywords

  • Calcium
  • Dyslipidemia
  • HMG-CoA reductase
  • Ionomycin
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet'. Together they form a unique fingerprint.

  • Cite this